Syntheses and Reactions of 1′,2′‐Unsaturated 2′,3′‐Seconucleoside Analogues

Abstract

AbstractThe 1′,2′‐unsaturated 2′,3′‐secoadenosine and 2′,3′‐secouridine analogues were synthesized by the regioselective elimination of the corresponding 2′,3′‐ditosylates, 2 and 18, respectively, under basic conditions. The observed regioselectivity may be explained by the higher acidity and, hence, preferential elimination of the anomeric H–C(1′) in comparison to HC(4′). The retained (tol‐4‐yl)sulfonyloxy group at C(3′) of 3 allowed the preparation of the 3′‐azido, 3′‐chloro, and 3′‐hydroxy derivatives 5–7 by nucleophilic substitution. ZnBr2 in dry CH2Cl2 was found to be successful in the removal (85%) of the trityl group without any cleavage of the acid‐sensitive, ketene‐derived N,O‐ketal function. In the uridine series, base‐promoted regioselective elimination (→19), nucleophilic displacement of the tosyl group by azide (→20), and debenzylation of the protected N(3)‐imide function gave 1′,2′‐unsaturated 5′‐O‐trityl‐3′‐azido‐secouridine derivative 21. The same compound was also obtained by the elimination performed on 2,2′‐anhydro‐3′‐azido‐3′‐azido‐3′‐deoxy‐5′‐O‐2′,3′‐secouridine (22) that reacted with KO(t‐Bu) under opening of the oxazole ring and double‐bond formation at C(1′).